Sodium hydride → 2-bromo-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine

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Reaction Conditions

Reaction Steps

In a dry round-bottomed flask, 2-bromo-5H-pyrrolo[2,3-b]pyrazine (5.0 g, 25.2 mmol) was dissolved in DMF (50 mL). The reaction mixture was cooled to 0° C. and sodium hydride (60% dispersion in mineral oil, 1.22 g, 30.6 mmol). The reaction mixture was warmed to room temperature and stirred for 15 min then cooled back to 0° C. and SEM-Cl (5.4 mL, 30.4 mmol) was slowly added. After the addition was complete, the ice bath was removed and the reaction mixture was stirred at room temperature for 1.5 h. The reaction mixture was quenched with 50 mL water and extracted with 150 mL diethyl ether (2×). The combined organic layers were washed twice with 30 mL water and once with 30 mL brine then dried over sodium sulfate, filtered and concentrated. The residue was absorbed on ˜20 g SiO2 and chromatographed over 200 g SiO2 with EtOAc/Hexanes (gradient: 0-15% EtOAc). All fractions containing product were combined and concentrated to afford 6.61 g (80%) of 2-bromo-5-(2-trimethylsilanylethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine as a pale yellow oil which gradually solidified. 1H NMR (CDCl3, 300 MHz): δ (ppm) 8.38 (s, 1H), 7.70 (d, J=3.8 Hz, 1H), 6.76 (d, J=3.8 Hz, 1H), 5.68 (s, 2H), 3.50-3.65 (m, 2H), 0.88-1.03 (m, 2H), 0.00 (s, 9H).

Provenance & Evidence